1. Field of the Invention
The present invention relates to the field of blood treatment devices having a blood purification element divided into two chambers by a semipermeable membrane, whose first chamber is part of a dialysis fluid loop and whose second chamber is part of an extracorporeal blood loop. The device has a dialysis fluid supply line for supplying fresh dialysis fluid to the first chamber and/or into the blood loop, a dialysis removal line for removing used dialysis fluid from the first chamber, a control unit for controlling the blood treatment device, an analysis unit, and at least one sensor, connected to the analysis unit, on at least one of the blood loop or dialysis fluid loop to detect the concentration of a first material which may penetrate the semipermeable membrane. The analysis unit is capable of determining the blood purification performance L1 of the blood purification element for the first material on the basis of the measurement values of the at least one sensor.
2. Description of the Prior Art
Various methods are used in kidney replacement treatment. In some of these methods, blood is continuously removed from a patient during the treatment and fed into an extracorporeal loop. There it flows through a blood purification element in order to then be returned to the patient. The blood purification element typically has a filter element divided into two chambers by a semipermeable membrane, one chamber of which blood flows through. Currently, filter elements which contain many thousands of hollow fibers, through which blood flows, are typically used above all for this purpose.
In hemodialysis, a purification fluid (dialysis fluid), which absorbs the materials such as urea to be removed from the blood by diffusion and, in regard to other materials such as electrolytes, which are to be left in the blood, has a composition similar to a healthy blood count, flows through the other chamber. Fluid volumes to be removed are also removed from the blood chamber to the dialysis fluid chamber of the filter element using a component which controls the ultrafiltration.
In hemofiltration, the other chamber of the filter element, which is referred to in the following as the first chamber, does not have a second fluid flowing through it completely. Rather, ultrafiltrate is only fed via the membrane into this chamber, which is then removed via an ultrafiltrate drain. In this case, the quantity of fluid removed is kept well over that which must be removed from the patient to achieve his dry weight. In this way, materials such as urea which are to be removed are carried off with the ultrafiltrate in an appreciable amount through convection. Simultaneously, almost the entire quantity of fluid is replaced by a substitution fluid which is returned to the patient at a suitable point via the extracorporeal loop.
Since convection and diffusion are able to remove molecules of different sizes through the membrane with different degrees of effectiveness, the combination of both methods in the form of a hemodiafiltration treatment is also used. For this purpose, modern dialysis machines offer the possibility of changing between these modes of treatment without complex modification being necessary. In this case, some known devices have the possibility of the dialysis and the substitution fluids being prepared online from water and appropriate concentrate by the machine during the treatment. For these devices, it is no longer necessary to keep ready enormous quantities of these fluids (up to approximately 200 liters) in the form of bags. Such a device is the object of European Patent Application 0 930 080 A1, for example.
In order to be able to monitor the success of kidney replacement treatment, the determination of treatment parameters on such blood purification devices, particularly the blood purification performance of the blood purification element, is of great interest. The clearance or dialysance of the blood purification element is typically specified as the blood purification performance.
The clearance K is defined as the blood flow which is completely freed of a substance (e.g., urea) by the blood purification element. In this case, it is assumed for a hemodialysis treatment that the dialysis fluid does not contain the substance to be removed when it enters the dialyzer. The clearance is a function of the area and material of the dialyzer and the particular operating conditions (blood flow, dialysis fluid flow, and ultrafiltration flow). The clearance occurs both through diffusion and through convection via the membrane of the filter element—the dialyzer.
The concept of clearance may also be expanded to substances such as sodium ions, for example, which are already present in the dialysis fluid. In this case, the term used is dialysance D. It is defined as the blood flow which is brought completely to the concentration level in the dialysis fluid.
The dimensionless variable Kt/V may be calculated from the clearance K, t being the duration of treatment and V being the distribution volume of the substance in the human body. Kt/V for urea is widely used as a measure for the efficiency of a dialysis treatment.
The measurement of the urea concentration is, however, relatively complicated. It either requires blood samples to be taken, which is unpleasant for the patient and in addition does not allow rapid, automated analysis, or it is still quite complicated as a measurement in the used dialysis fluid.
A current alternative is the determination of the ionic dialysance. The basic principle of these measurements is based on the fact that urea and small ions such as Na+, etc. have nearly identical diffusion behaviors. The concentration of these ions may be determined easily in the dialysis fluid with the aid of measurements of the electrical conductivity, which may be determined using relatively simply constructed measurement cells. Instead of the urea clearance, therefore, the ionic dialysance is primarily determined. This may then be set equal to the urea clearance, due to the identical diffusion behavior to be expected.
Since, for hemodialysis, the clearance only represents a special case of dialysance for the case in which the relevant substance is not present in the dialysis fluid, it is to be included as synonymous with the term dialysance in the following.
In the related art, there are diverse publications on the calculation of dialysance (e.g., J. Sargent and F. Gotch, in: Replacement of Renal Functions by Dialysis, 4th edition, edited by C. Jacobs et al., Kluwer, Dordrecht, 1996, p. 39 et seq.). Without ultrafiltration, it may be expressed in the dialysate-side form in the following form:
                              D          =                      Qd            ⁢                                          Cdo                -                Cdi                                                              α                  ⁢                                                                          ⁢                  Cbi                                -                Cdi                                                    ,                            (        1        )            in which    Qd: dialysis fluid flow,    Cdo: concentration of the material observed in the dialysis fluid removed,    Cdi: concentration of the material observed in the dialysis fluid supplied,    Cbi: concentration of the material observed in the blood flowing in the extracorporeal loop (only the volume component in which this material is effectively dissolved to be observed),    α: Gibbs-Donnan factor.
The Gibbs-Donnan factor takes the fact into consideration that on the blood side, charged ions such as Na+ are partially bound on oppositely charged proteins, which are not accessible to the dialyzer. This effect has the result that in the diffusive equilibrium (with vanishing flows) in the blood plasma, a somewhat higher ion concentration would result than in the dialysis fluid, since an electrical field counteracts the diffusion. For the case, which is especially relevant in practice, of sodium ions in blood plasma, a is approximately 0.95. If precision is not required, this factor may also be ignored.
In equation 1, all dimensions except for Cbi may be measured easily. For this purpose, it is sufficient to position two conductivity measurement cells in the dialysis fluid loop, which each determine the conductivities at the inlet and outlet of the dialyzer. The latter may be easily converted into the concentrations Cdi and Cdo. If the concentration Cdi is also preset and therefore known, because precisely defined fluids are used, for example, the measurement of Cdi may even be unnecessary. The dialysis fluid flow Qd is typically preset by the hemodialysis machine and is therefore also known. Otherwise, additional appropriate sensors may also be provided, of course.
However, conductivity measurements on the blood side are problematic for practical reasons. It is nonetheless possible to eliminate the term Cbi by changing the concentration Cdi. This may be performed in the form of a concentration step or a bolus, for example. The first is described in German Patent Application 39 38 662 A1, and the latter in German Patent Application 197 47 360 A1 or WO 00/02604 A1 (explicit reference is hereby made to these publications). Both possibilities are to be considered in the following as alternatives for a change of the concentration in a fresh fluid which is necessary for the blood treatment. The dialysance may then be determined as follows:
                              D          =                                    Qd              ⁡                              (                                  1                  -                                                                                    Cdo                        ⁢                                                                                                  ⁢                        2                                            -                                              Cdo                        ⁢                                                                                                  ⁢                        1                                                                                                            Cdi                        ⁢                                                                                                  ⁢                        2                                            -                                              Cdi                        ⁢                                                                                                  ⁢                        1                                                                                            )                                      =                          Qd              ⁡                              (                                  1                  -                                                            Δ                      ⁢                                                                                          ⁢                      Cdo                                                              Δ                      ⁢                                                                                          ⁢                      Cdi                                                                      )                                                    ,                            (        2        )            in which    Cdi1,2: Cdi before and after (step) or outside and during (bolus) the change    Cdo1,2: Cdo before and after (step) or outside and during (bolus) the change.
In the case of a step change, ΔCdi and/or ΔCdo represent simple differences, in the case of the bolus method, they are understood as the change relative to a base level integrated over the bolus.
With the aid of D, Cbi may now also be determined using equation (1). In this case, it would be considered equivalent to first determine Cbi as the parameter to be determined from an equation corresponding to the equation (2), which arises from equation (1) if D is eliminated.
Further methods are known in the related art, such as in WO 98/32476 A1 or European Patent Application 0 658 352 A1, which do not explicitly use the equation (2) to determine D, but are, in the final analysis, always based on the principle of producing a change of a physical-chemical property Cdi and retaining the corresponding change Cdo in order to obtain information about the physical-chemical property Cbi on the blood side or the blood purification performance D.
Sometimes, the mass exchange or filter coefficient k0A, which has a fixed relationship to the dialysance D, is also used for describing the blood purification performance of a blood purification element such as a dialyzer. The coefficient k0A is determined solely by the material observed and the dialyzer membrane used, but not by treatment parameters such as blood flow, dialysis fluid flow, or ultrafiltration flow. It is the product of the parameter k0, which is a function of the membrane, and the total area of the membrane A. In this case, k0 corresponds to the diffusion flow of the material observed per area unit of the membrane, divided by the concentration gradient on the membrane. K0A may then be interpreted as the maximum possible dialysance in the ideal case of purely diffusive transport with infinitely large dialysis fluid flow and blood flow.
The coefficient k0A for a material may be determined on the basis of the measurement of the dialysance D according to equation (3):
                              k          ⁢                                          ⁢          0          ⁢          A                =                              QbQd                          Qd              -              Qb                                ⁢          ln          ⁢                                    Qb              ⁡                              (                                  D                  -                  Qd                                )                                                    Qd              ⁡                              (                                  D                  -                  Qb                                )                                                                        (        3        )            
In the related art, methods which allow determination during a hemodialysis treatment are specified exclusively in this case. There are also statements therein—sometimes differing—as to how the ultrafiltration flow Qf withdrawn from the blood during a hemodialysis treatment may be taken into consideration in the equations (1) or (2). An example of this is European Patent Application 1 062 960 A2, according to which Qd is replaced by the sum of the flows Qd and Qf. However, for a hemodialysis treatment the ultrafiltration flow Qf is very small in comparison to the dialysis fluid flow Qd and also to the blood flow Qb, i.e., it is a relatively small interfering effect. Thus, for example, typical values are Qf=15 ml/minute, Qd=500 ml/minute, and Qb=300 ml/minute.
Similar restrictions apply for the blood flow Qb in equation (3) as for the concentration Cbi in equation (1). Sometimes, only the volume component of the blood in which the material observed is effectively dissolved must be considered in equation (3). Depending on the material, this may be the blood water component with or without blood cells, for example. The ways of deriving the component flow in relation to the complete blood flow on the basis of average, assumed, or measured data via the blood composition (hematocrit, proteins, etc.) are sufficiently known to one skilled in the art in this case (e.g., J. Sargent and F. Gotch, in: Replacement of Renal Functions by Dialysis, 4th edition, edited by C. Jacobs et al., Kluwer, Dordrecht, 1996, p. 41 et seq.), so that further explanation will be dispensed with at this point.
However, for kidney replacement treatment, the knowledge of the performance of the blood purification element is just as much of interest when it is a hemofiltration treatment—whether alone or in combination with a hemodialysis treatment in the form of a hemodiafiltration treatment.
As was described in the previously filed German Patent Application 10212247.4, to the content of whose disclosure explicit reference is made here, methods developed for hemodialysis may be transferred to hemofiltration and hemodiafiltration if the dialysis fluid flow Qd includes the substitution fluid flow and the concentration for the fresh dialysis fluid is equal to the concentration for the substitution fluid. In this case, the dialysis fluid flow Qd in the equations (1) and (2) is to be set to the sum of the flow of dialysis fluid flowing in the first chamber of the hemodialyzer, the flow Qs of the substitution fluid, and the total ultrafiltration flow Qf to be withdrawn from the blood.
Using the previously known methods, it is possible—as described above—to determine the concentration Cbi of a first material in the blood flowing into the blood purification unit and/or to determine the blood purification performance of the blood purification unit on the basis of concentration measurements in the dialysis fluid, the concentration of the first material in the dialysis fluid having to be changed during the method, however. This requires a certain minimum measurement time for the corresponding adjustment or change of the concentration. It is especially disadvantageous that, using these methods, materials which do not generally occur in the fresh dialysis fluid (e.g. creatinine or phosphate) or whose variation may be critical to patient compatibility (e.g., potassium), are not accessible.
Other methods are known, like that described in U.S. Pat. No. 6,126,831, in which, for dialysate measurement of blood components, the dialysis fluid is slowed or even stopped in such a way that the concentration of both fluid equalizes, so that the concentration in the dialysis fluid corresponds directly to the concentration Cbi in the blood. Methods of this type are also time-consuming and require direct intervention in the blood treatment.
The present invention is therefore based on the object of providing a device which, without additional intervention in the blood treatment performed using a blood purification element, allows determination of a further, different blood purification performance of the blood purification element in relation to a further material and therefore opens up the possibility of also determining the blood concentration of this further material.